This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To understand differences in MHC genetics, especially since cynomolgus macaques are increasingly used for biodefense and AIDS research. We have recently discovered that cynomolgus macaques from different geographical locations have distinct major histocompatibility complex (MHC) genetics. In this project, we are defining the MHC genetics of cynomolgus macaques from five geographic origins, developing genetic tests, and defining peptide-binding motifs from common MHC alleles. This new subproject initiated in September 2005. Since the inception of this project, we have collected samples from Mauritian, Indonesian, Vietnamese, Filipino, and Chinese cynomolgus macaques. We are using a combination of approaches to identify the MHC genes present in each population of monkeys. High-throughput DNA sequencing of selected animals identified hundreds of MHC class I alleles, dramatically expanding the database of known alleles. Peptide binding motifs have been determined for six of these alleles by Edman degradation. The approaches developed in this proposal are proving valuable for studies of non-cynomolgus macaques. Two of these methods, microsatellite mapping and reference strand mediated conformational analysis (RSCA), are now being applied to rhesus and pigtailed macaques. This research used WNPRC Animal Services, Immunology &Virology Services, and Genetics Services. Funding ended before this reporting period. Numerous publications have resulted.